In the United States, for the first time, a human being received a pig kidney without an immediate rejection being triggered in his immune system. The feat encourages research associated with the University of São Paulo (USP), with similar line and commanded by Silvano Ray, pioneer of liver transplantation in Latin America. The surgeon expects to carry out the first tests with human beings in the country in two years, if the study obtains an investment to build a biosafety breeding facility (pig facility).
“As much as the laboratory data indicated that we were on the right path, there were skeptics. The fact of having succeeded demonstrates that this line of research is promising”, evaluates the surgeon. For geneticist Mayana Zatz, also involved in the research, the American success facilitates the approval of experiments by Brazilian ethics committees. “It’s important in the sense of showing: ‘Look, it’s already being done in the US’.”
The Brazilian study, carried out at USP’s Center for Research on the Human Genome and Stem Cells, where a laboratory for xenotransplantation (transplantation between different species) was created, was conceived by Raia four years ago. The initiative was supported by the Foundation for Research Support of the State of São Paulo (Fapesp) and the pharmaceutical company EMS. The genetic engineering part, according to the scientists, consists of inactivating pig genes and adding human genes, performed with the CRISPR/Cas9 technique (in the method, Cas9, an enzyme in the bacterial defense system, together with an RNA , used as a guide, cuts the stretch of interest from a DNA). Thus, it was possible to create genetically modified embryos, which need to be introduced into a matrix and raised in the pig facility.
Raia says that the first offspring will be bred in a common vivarium at the USP Medical School. From then on, pre-clinical tests will be performed in isolated perfusion, a system that allows the preservation of organs from donor collection to transplantation. The so-called preservation liquid (perfusate) is usually used. The experiment will, however, use human blood as a perfusate. “If the perfusion of the genetically modified kidney with human blood, for 12 hours, does not demonstrate rejection in both organ and perfusate biopsies, it will be demonstrated that our product is suitable to be transplanted in patients”, declares the surgeon.
With clinical trials, it will also be possible to find out whether the pig’s kidney will be used permanently or temporarily, until a compatible human organ is available, according to Mayana. The geneticist says that the intention is, in the future, also to successfully transplant the heart, skin and cornea, for example, from pigs to humans.
With the population aging trend, concerns about transplants and waiting lists increase. Until June of this year, 26,230 Brazilians were on the waiting list for a kidney, according to the Brazilian Association of Organ Transplants (ABTO).
With this, the scientific community, in the last decade, has focused on what it calls “additional organs”, which do not come from corpses or volunteers. “Among these techniques, the most promising is xenotransplantation (transplantation between two different species)”, says Raia. Pigs, above all, are more suitable for three reasons. “They have digestive and circulatory physiology very similar to ours, have a shorter gestation time and are prolific.”
The transplantation of a common pig, without modified genes, however, creates a hyperacute rejection of the human immune system, which occurs minutes after grafting, followed by a disseminated thrombosis in the transplant vessels and graft necrosis, requiring immediate explantation.
In the context of xenotransplantation, the kidney is always the first organ targeted by researchers. This is due to the possibility of keeping the patient on hemodialysis, in case something goes wrong. “When a patient has irreversible renal failure, he does not die, he goes on hemodialysis and survives thanks to the machine, to the artificial ‘kidney'”, says Silvano Raia.
He says that for a long time, while porcine xenotransplantation was being studied, “a fair concern” was raised about the possibility of infecting humans with viruses that are harmless to pigs. However, the fears fell to the ground when the possibility of inactivating them was discovered.